Author + information
- aDepartment of Cardiac Surgery, Heart Hospital Baylor Plano, Baylor Scott & White Health, Dallas, Texas
- bDepartment of Cardiology, Baylor University Medical Center, Baylor Scott & White Health, Dallas, Texas
- ↵∗Address for correspondence:
Dr. Michael Mack, Baylor Scott & White Health, 1100 Allied Drive, Plano, Texas 75075.
- medical futility
- risk assessment
- surgical aortic valve replacement
- transcatheter aortic valve replacement
Frailty is a relatively common condition in patients with cardiovascular disease. This condition, which includes impairment of multiple physiological systems, occurs more frequently with advancing age and is particularly relevant when these patients undergo cardiovascular interventions or surgery. As a general rule of thumb, the more invasive the procedure and the older the patient, the more that frailty matters in terms of influencing procedure outcomes, recovery, and benefit. There are multiple risk models that have accuracy in predicting early, 30-day outcomes after surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR) (1,2). Although a wide spectrum of patient factors and comorbid disease conditions are used as covariates in constructing these predictive algorithms, measures of frailty have not been routinely included. The reasons for lack of inclusion include the wide variety of tools available to measure frailty, a lack of a consensus on which tools to use, and the burden and time required to perform the tests, leading to variability and incompleteness of collection. In addition, routine use has been hampered by the lack of a solid evidence base for the measurement of frailty really having value in determining the ability of a patient to undergo a procedure successfully and withstand the associated systemic and physiological insults that may preclude full recovery. However, with the advent of less-invasive procedures, which offer treatment options to patients previously not considered candidates, measurement of frailty in the elderly population has assumed greater import. The 2014 American Heart Association/American College of Cardiology Guideline for the Management of Patients with Valvular Heart Disease (3) included frailty, major organ system dysfunction, and procedure-specific impediments as adjunctive to the Society of Thoracic Surgeons Predicted Risk of Mortality (STS PROM) in risk assessment in patients under consideration for treatment (4). The tools most commonly used in current clinical evaluation of patients with aortic stenosis are the measurement of gait speed using the 5-m walk test and the Fried Criteria, which measure 4 domains of frailty, including mobility, strength, nutritional status, and habitual activity.
With this background in mind, in this issue of the Journal, the investigators of the FRAILTY-AVR (Frailty Assessment Before Cardiac Surgery & Transcatheter Interventions) study prospectively evaluated the incremental value of 7 different frailty scales to a standard risk algorithm in predicting poor outcomes following TAVR and SAVR (5). Of note is that the investigators are experts both in interventions for aortic stenosis and, even more importantly, in the field of frailty and its measurement. They evaluated 1,020 patients (646 patients undergoing TAVR and 374 undergoing SAVR) at 14 centers in 3 countries over a 5-year period using commonly used frailty measurement tools including Fried, Fried+, Rockwood, Short Physical Performance Battery, Bern, Columbia, and the Essential Frailty Toolset (EFT). Frailty scales were dichotomized on the basis of original cutoffs for all 7 tools. The prevalence of frailty varied between 26% and 68%, depending on the particular tool used. The primary outcome was death at 1 year, with 30-day mortality and death and disability 1 year after the procedure as secondary endpoints.
The results of the FRAILTY-AVR trial demonstrated that the EFT had the highest predictive value for death at 1 year (adjusted odds ratio [OR]: 3.72; 95% confidence interval [CI]: 2.54 to 5.45), was the strongest predictor of worsening disability at 1 year (adjusted OR: 2.13; 95% CI: 1.57 to 2.87) as well as death at 30 days (adjusted OR: 3.29; 95% CI: 1.73 to 6.26). Moreover, EFT added significant incremental value to STS PROM in predicting 1-year mortality, with a final C-statistic of 0.813. The results held true for both TAVR and SAVR.
EFT is a relatively simple tool that is neither particularly burdensome nor time-consuming, and captures multiple domains of frailty including lower-extremity weakness, cognitive impairment, and malnutrition. The test consists of 4 items for a composite score of 0 to 5, with 5 being most frail: time to stand 5 times from a seated position without using arms (1 point if ≥15 s, 2 points if unable to complete), cognition (1 point if Mini-Mental State Examination [MMSE] score <24), hemoglobin (1 point if <13 g/dl in men or <12 g/dl in women), and serum albumin (1 point if <3.5 g/dl). Frailty is defined as ≥3 of 5 points, with severe frailty defined as 5 of 5. A shortened version of the MMSE, which is the most time-consuming portion of the toolset, is being developed by the investigators.
What do we learn from the FRAILTY-AVR study and how is it likely to influence practice?
1. Frailty can be measured by a relatively simple tool that captures multiple domains without being unduly burdensome.
2. Presence of frailty is predictive of 1-year death after treatment of aortic stenosis.
3. Frailty, as measured by EFT, is additive to the STS PROM in predicting 1-year mortality.
4. Measurement of frailty with the EFT is also predictive of 30-day mortality and 1-year mortality and disability.
5. The EFT appears to be valid for both TAVR and SAVR.
The findings of this study add a significant tool to the clinical armamentarium for evaluating the ability of a patient to benefit and recover from a procedure to correct aortic stenosis. These findings, of course, are limited to this particular patient cohort, at this particular time, treated by these investigators. Validation of these findings by other investigators and in other patient populations, with this and other risk profiles, with aortic stenosis is, of course, necessary. Whether EFT is accurate with other disease treatments and in populations where the incidence of frailty is less is also unknown. Nonetheless, this study is an important step forward in determining which patients are unlikely to benefit, in terms of both survival and improved quality of life, after treatment of their aortic stenosis.
Futility or lack of improvement in survival and/or quality of life after correcting aortic stenosis has been the subject of intense interest. Arnold et al. (6) have demonstrated that among 2,830 patients who underwent TAVR in the CoreValve U.S. Pivotal Extreme and High Risk trials and associated continued access registries, 50.8% of patients experienced a poor outcome at 1 year (death 30.2%; poor quality of life 19.6%). In the PARTNER (Placement of Aortic Transcatheter Valve) 1B trial, approximately one-half of inoperable patients did not survive or have an improved quality of life at 1 year (7). One-year mortality in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry is 21.6% at 1 year (8). The findings from this and other studies are beginning to give us a better handle on who exactly are those futile patients who should not be treated, either because they will not be alive at 1 year or, if they are, they will have increasing disability, worse quality of life, and/or institutionalization. Those patients include frail patients, as determined by EFT, especially the severely frail, defined as scoring 5 of 5, who have an 80% chance of being dead or disabled at 1 year post-procedure. Other factors from this and other studies associated with poor outcomes at 1 year include atrial fibrillation, oxygen-dependent pulmonary disease, severe tricuspid regurgitation, sarcopenia, immobility, inability to live independently, cognitive impairment, and renal failure, especially when dialysis-dependent. None of these factors alone should, of course, preclude patients who, in the judgment of the treating clinicians, are likely to receive benefit from treating their aortic stenosis. However, the results of this study, taken in conjunction with the emergence of findings of other studies, are giving us a better definition of which patients are likely to benefit from treatment and, even more importantly, those who are not. These factors, which include frailty assessment, should be important components of informed consent in a patient-centric shared decision-making discussion by each treating center’s heart team. One of the most difficult tasks in medicine is knowing when a treatment is futile and how to effectively communicate that to patients and their families. This study has given us greater insight into the assessment and measurement of frailty, and given us a less burdensome tool with a high degree of probability to predict early and midterm outcomes of the treatment of aortic stenosis. The investigators have demonstrated that the measurement of frailty really does matter.
↵∗ Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Dr. Mack is an uncompensated co-principal investigator for the PARTNER 3 trial for Edwards Lifesciences and the COAPT trial for Abbott Vascular; and serves (uncompensated) on the executive committee for the Intrepid trial for Medtronic. Dr. Stoler has received honoraria for serving on the advisory board and as a TAVR proctor for Medtronic and Boston Scientific.
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